Ultralight, Robust, Thermal Insulating Silica Nanolace Aerogels Derived from Pickering Emulsion Templates.

Synthesis of silica aerogel insulators with ultralight weight and strong mechanical properties using a simplified technique remains challenging for functional soft materials. This study introduces a promising method for the fabrication of mechanically reinforced ultralight silica aerogels by employing attractive silica nanolace (ASNLs)-armored Pickering emulsion templates. For this, silica nanolaces (SiNLs) are fabricated by surrounding a cellulose nanofiber with necklace-shaped silica nanospheres. In order to achieve amphiphilicity, which is crucial for the stabilization of oil-in-water Pickering emulsions, hydrophobic alkyl chains and hydrophilic amine groups are grafted onto the surface of SiNLs by silica coupling reactions. Freeze-drying of ASNLs-armored Pickering emulsions has established a new type of aerogel system. The ASNLs-supported mesoporous aerogel shows 3-fold greater compressive strength, 4-fold reduced heat transfer, and a swift heat dissipation profile compared to that of the bare ASNL aerogel. Additionally, the ASNL aerogel achieves an ultralow density of 8 mg cm-3, attributed to the pore architecture generated from closely jammed emulsion drops. These results show the potential of the ASNL aerogel system, which is ultralight, mechanically stable, and thermally insulating and could be used in building services, energy-saving technologies, and the aerospace industry.

Amine-assisted catechol-based nanocoating on ultrasmall iron oxide nanoparticles for high-resolution T1 angiography.

Surface engineered iron oxide nanoparticles (IONPs) with catecholic ligands have been investigated as alternative T1 contrast agents. However, complex oxidative chemistry of catechol during IONP ligand exchange causes surface etching, heterogeneous hydrodynamic size distribution, and low colloidal stability because of Fe3+ mediated ligand oxidation. Herein, we report highly stable and compact (∼10 nm) Fe3+ rich ultrasmall IONPs functionalized with a multidentate catechol-based polyethylene glycol polymer ligand through amine-assisted catecholic nanocoating. The IONPs exhibit excellent stability over a broad range of pHs and low nonspecific binding in vitro. We also demonstrate that the resultant NPs have a long circulation time (∼80 min), enabling high resolution T1 magnetic resonance angiography in vivo. These results suggest that the amine assisted catechol-based nanocoating opens a new potential of metal oxide NPs to take a step forward in exquisite bio-application fields.

Correspondence between development of cytotoxic edema and cerebrospinal fluid volume and flow in the third ventricle after ischemic stroke.

OBJECTIVES: The importance of monitoring cerebrospinal fluid for the development of edema in ischemic stroke has been emphasized; however, studies on the relationship between intraventricular cerebrospinal fluid behavior and edema through longitudinal observations and analysis are rare. This study aimed to investigate the correlation between the development of cytotoxic edema and cerebrospinal fluid volume and flow in the third ventricle after ischemic stroke. MATERIALS AND METHODS: The ventricle and edema regions were obtained using apparent diffusion coefficients and T2 and subdivided into lateral/ventral 3rd ventricles and cytotoxic/vasogenic (or cyst) edema, respectively. In rat models of ischemic stroke, the volume and flow (via the pseudo-diffusion coefficient [D*]) of the ventricles and edema volumes were longitudinally monitored for up to 45 days after surgery. RESULTS: The volume of cytotoxic edema increased in the hyperacute and acute phases, whereas the volume (r = -0.49) and median D* values (r = -0.48 in the anterior-posterior direction) of the ventral 3rd ventricle both decreased, showing negative correlations with the volume of cytotoxic edema. In contrast, the volume of vasogenic edema/cyst was positively correlated with the volume (r = 0.73) and median D* values (r = 0.78 in the anterior-posterior direction) of the lateral ventricle in the subacute and chronic phases. CONCLUSIONS: This study showed that the evolution of cerebrospinal fluid volume and flow in the ventricles was associated with edema progression at different time points in the ischemic stroke brain. This provides an efficient framework for monitoring and quantifying the interplay between cerebrospinal fluid and edema.

Improved laminar specificity and sensitivity by combining SE and GE BOLD signals.

The most widely used gradient-echo (GE) blood oxygenation level-dependent (BOLD) contrast has high sensitivity, but low specificity due to draining vein contributions, while spin-echo (SE) BOLD approach at ultra-high magnetic fields is highly specific to neural active sites but has lower sensitivity. To obtain high specificity and sensitivity, we propose to utilize a vessel-size-sensitive filter to the GE-BOLD signal, which suppresses macrovascular contributions and to combine selectively retained microvascular GE-BOLD signals with the SE-BOLD signals. To investigate our proposed idea, fMRI with 0.8 mm isotropic resolution was performed on the primary motor and sensory cortices in humans at 7 T by implementing spin- and gradient-echo (SAGE) echo planar imaging (EPI) acquisition. Microvascular-passed sigmoidal filters were designed based upon the vessel-size-sensitive ΔR2*/ΔR2 value for retaining GE-BOLD signals originating from venous vessels with ≤ 45 µm and ≤ 65 µm diameter. Unlike GE-BOLD fMRI, the laminar profile of SAGE-BOLD fMRI with the vessel-size-sensitive filter peaked at ∼ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity over GE-BOLD fMRI. Also, the functional sensitivity of SAGE BOLD at middle layers (0.75-1.5 mm) was improved by ∼ 80% to ∼100% when compared with SE BOLD. In summary, we showed that combined GE- and SE-BOLD fMRI with the vessel-size-sensitive filter indeed yielded improved laminar specificity and sensitivity and is therefore an excellent tool for high spatial resolution ultra-high filed (UHF)-fMRI studies for resolving mesoscopic functional units.

Efficient Segmentation for Left Atrium With Convolution Neural Network Based on Active Learning in Late Gadolinium Enhancement Magnetic Resonance Imaging.

BACKGROUND: To propose fully automatic segmentation of left atrium using active learning with limited dataset in late gadolinium enhancement in cardiac magnetic resonance imaging (LGE-CMRI). METHODS: An active learning framework was developed to segment the left atrium in cardiac LGE-CMRI. Patients (n = 98) with atrial fibrillation from the Korea University Anam Hospital were enrolled. First, 20 cases were delineated for ground truths by two experts and used for training a draft model. Second, the 20 cases from the first step and 50 new cases, corrected in a human-in-the-loop manner after predicting using the draft model, were used to train the next model; all 98 cases (70 cases from the second step and 28 new cases) were trained. An additional 20 LGE-CMRI were evaluated in each step. RESULTS: The Dice coefficients for the three steps were 0.85 ± 0.06, 0.89 ± 0.02, and 0.90 ± 0.02, respectively. The biases (95% confidence interval) in the Bland-Altman plots of each step were 6.36% (-14.90-27.61), 6.21% (-9.62-22.03), and 2.68% (-8.57-13.93). Deep active learning-based annotation times were 218 ± 31 seconds, 36.70 ± 18 seconds, and 36.56 ± 15 seconds, respectively. CONCLUSION: Deep active learning reduced annotation time and enabled efficient training on limited LGE-CMRI.

Automated volumetric determination of high R2 * regions in substantia nigra: A feasibility study of quantifying substantia nigra atrophy in progressive supranuclear palsy.

The establishment of an unbiased protocol for the automated volumetric measurement of iron-rich regions in the substantia nigra (SN) is clinically important for diagnosing neurodegenerative diseases exhibiting midbrain atrophy, such as progressive supranuclear palsy (PSP). This study aimed to automatically quantify the volume and surface properties of the iron-rich 3D regions in the SN using the quantitative MRI-R2 * map. Three hundred and sixty-seven slices of R2 * map and susceptibility-weighted imaging (SWI) at 3-T MRI from healthy control (HC) individuals and Parkinson's disease (PD) patients were used to train customized U-net++ convolutional neural network based on expert-segmented masks. Age- and sex-matched participants were selected from HC, PD, and PSP groups to automate the volumetric determination of iron-rich areas in the SN. Dice similarity coefficient values between expert-segmented and detected masks from the proposed network were 0.91 ± 0.07 for R2 * maps and 0.89 ± 0.08 for SWI. Reductions in iron-rich SN volume from the R2 * map (SWI) were observed in PSP with area under the receiver operating characteristic curve values of 0.96 (0.89) and 0.98 (0.92) compared with HC and PD, respectively. The mean curvature of the PSP showed SN deformation along the side closer to the red nucleus. We demonstrated the automated volumetric measurement of iron-rich regions in the SN using deep learning can quantify the SN atrophy in PSP compared with PD and HC.

D* from diffusion MRI reveals a correspondence between ventricular cerebrospinal fluid volume and flow in the ischemic rodent model.

Quantitative measurement of cerebrospinal fluid (CSF) flow and volume and longitudinal monitoring of CSF dynamics provide insights into the compensatory characteristics of post-stroke CSF. In this study, we compared the MRI pseudo-diffusion index (D*) of live and sacrificed rat brains to confirm the effect of ventricular CSF flow on diffusion signals. We observed the relationship between the CSF peak velocities and D* through Monte Carlo (MC) simulations to further understand the source of D* contrast. We also determined the dominant CSF flow using D* in three directions. Finally, we investigated the dynamic evolutions of ventricular CSF flow and volume in a stroke rat model (n = 8) from preoperative to up to 45 days after surgery and determined the correlation between ventricular CSF volume and flow. MC simulations showed a strong positive correlation between the CSF peak velocity and D* (r = 0.99). The dominant CSF flow variations in the 3D ventricle could be measured using the maximum D* map. A longitudinal positive correlation between ventricular CSF volume and D* was observed in the lateral (r = 0.74) and ventral-third (r = 0.81) ventricles, respectively. The directional D* measurements provide quantitative CSF volume and flow information, which would provide useful insights into ischemic stroke with diffusion MRI.

Differential Effect of Iron and Myelin on Susceptibility MRI in the Substantia Nigra.

Background The heterogeneous composition of substantia nigra (SN), including iron, nigrosome-1 substructure, and myelinated white matter, complicates the interpretation of MRI signals. Purpose To investigate R2* and quantitative susceptibility mapping (QSM) in the SN subdivisions of participants with Parkinson disease and healthy control subjects. Materials and Methods In this prospective study conducted from November 2018 to November 2019, participants with Parkinson disease and sex-matched healthy control subjects underwent 3-T MRI. R2* and QSM values were measured and compared in the anterior SN and posterior SN at the rostral (superior) and caudal (inferior) levels. Postmortem MRI and histology correlation of midbrain tissues was evaluated to investigate the effect of myelin and iron in the SN on R2* and QSM values. Results Forty individuals were evaluated: 20 healthy control subjects (mean age, 61 years ± 3 [standard deviation]; 10 men) and 20 participants with Parkinson disease (mean age, 61 years ± 4; 10 men). The R2* values of participants with Parkinson disease were higher in all subdivisions of the SN compared with R2* values in healthy control subjects (all P < .05). For QSM, no evidence of a difference was found in the rostral posterior SN (healthy control subjects, 54.1 ppb ± 21.0; Parkinson disease, 62.2 ppb ± 19.8; P = .49). The combination of rostral R2* and caudal QSM values resulted in an area under the receiver operating characteristic curve of 0.84. R2* values showed higher correlation with QSM values at the caudal level than at the rostral level within each group (all P < .001). Postmortem investigation demonstrated that R2* and QSM values showed weak correlation in the myelin-rich areas (r = 0.22 and r = 0.36, P < .001) and strong correlation in myelin-scanty areas (r ranged from approximately 0.52 to approximately 0.78, P < .001) in the SN. Conclusion Considering the iron and myelin distribution in the substantia nigra subdivisions, the subdivisional analysis of substantia nigra using R2* and quantitative susceptibility mapping might aid in specifically differentiating individuals with Parkinson disease from healthy control subjects. © RSNA, 2021 Online supplemental material is available for this article.

MRI investigation of vascular remodeling for heterogeneous edema lesions in subacute ischemic stroke rat models: Correspondence between cerebral vessel structure and function.

The spatial heterogeneity in the temporal occurrence of pseudo-normalization of MR apparent diffusion coefficient values for ischemic lesions may be related to morphological and functional vascular remodeling. As the area of accelerated pseudo-normalization tends to expand faster and more extensively into the chronic stage, detailed vascular characterization of such areas is necessary. During the subacute stage of transient middle cerebral artery occlusion rat models, the morphological size of the macrovasculature, microvascular vessel size index (VSI), and microvessel density (MVD) were quantified along with functional perfusion measurements of the relative cerebral blood flow (rCBF) and mean transit time (rMTT) of the corresponding areas (33 cases for each parameter). When compared with typical pseudo-normalization lesions, early pseudo-normalization lesions exhibited larger VSI and rCBF (p < 0.001) at reperfusion days 4 and 7, along with reduced MVD and elongated rMTT (p < 0.001) at reperfusion days 1, 4, and 7. The group median VSI and rCBF exhibited a strong positive correlation (r = 0.92), and the corresponding MVD and rMTT showed a negative correlation (r = -0.48). Light sheet fluorescence microscopy images were used to quantitatively validate the corresponding MRI-derived microvascular size, density, and cerebral blood volume.

Improvement of sensitivity and specificity for laminar BOLD fMRI with double spin-echo EPI in humans at 7 T.

Mapping mesoscopic cortical functional units such as columns or laminae is increasingly pursued by ultra-high field (UHF) functional magnetic resonance imaging (fMRI). The most popular approach for high-resolution fMRI is currently gradient-echo (GE) blood oxygenation level-dependent (BOLD) fMRI. However, its spatial accuracy is reduced due to its sensitivity to draining vessels, including pial veins, whereas spin-echo (SE) BOLD signal is expected to have higher spatial accuracy, albeit with lower sensitivity than the GE-BOLD signal. Here, we introduce a new double spin-echo (dSE) echo-planar imaging (EPI) method to improve the sensitivity of SE-BOLD contrast by averaging two spin-echoes using three radiofrequency pulses. Human fMRI experiments were performed with slices perpendicular to the central sulcus between motor and sensory cortices at 7 T during fist-clenching with touching. First, we evaluated the feasibility of single-shot dSE-EPI for BOLD fMRI with 1.5 mm isotropic resolution and found that dSE-BOLD fMRI has higher signal-to-noise ratio (SNR), temporal SNR (tSNR), and higher functional sensitivity than conventional SE-BOLD fMRI. Second, to investigate the laminar specificity of dSE-BOLD fMRI, we implemented a multi-shot approach to achieve 0.8-mm isotropic resolution with sliding-window reconstruction. Unlike GE-BOLD fMRI, the cortical profile of dSE-BOLD fMRI peaked at ~ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity in humans over GE-BOLD fMRI. The proposed multi-shot dSE-EPI method is viable for high spatial resolution UHF-fMRI studies in the pursuit of resolving mesoscopic functional units.

Target-switchable Gd(III)-DOTA/protein cage nanoparticle conjugates with multiple targeting affibody molecules as target selective T1 contrast agents for high-field MRI.

Magnetic resonance imaging (MRI) is a non-invasive in vivo imaging tool, providing high enough spatial resolution to obtain both the anatomical and the physiological information of patients. However, MRI generally suffers from relatively low sensitivity often requiring the aid of contrast agents (CA) to enhance the contrast of vessels and/or the tissues of interest from the background. The targeted delivery of diagnostic probes to the specific lesion is a powerful approach for early diagnosis and signal enhancement leading to the effective treatment of various diseases. Here, we established targeting ligand switchable nanoplatforms using lumazine synthase protein cage nanoparticles derived from Aquifex aeolicus (AaLS) by genetically introducing the SpyTag peptide (ST) to the C-terminus of the AaLS subunits to form an ST-displaying AaLS (AaLS-ST). Conversely, multiple targeting ligands were constructed by genetically fusing SpyCatcher protein (SC) to either HER2 or EGFR targeting affibody molecules (SC-HER2Afb or SC-EGFRAfb). Gd(III)-DOTA complexes were chemically attached to the AaLS-ST and the external surface of the Gd(III)-DOTA conjugated AaLS-ST (Gd(III)-DOTA-AaLS-ST) were successfully decorated with either the HER2Afb or the EGFRAfb. The resulting Gd(III)-DOTA-AaLS/HER2Afb and Gd(III)-DOTA-AaLS/EGFR2Afb exhibited high r1 relaxivity values of 57 and 25 mM-1 s-1 at 1.4 and 7 T, respectively, which were 10-fold or higher than those of the clinically used Dotarem. Their target-selective contrast enhancements were confirmed with in vitro cell-based MRI scans and the in vivo MR imaging of tumor-bearing mouse models at 7 T. A target-switchable AaLS-based nanoplatform that was developed in this study might serve as a promising T1 CA developing platform at a high magnetic field to detect various tumor sites in a target-specific manner in future clinical applications.

Iron accumulation in the oculomotor nerve of the progressive supranuclear palsy brain.

Abnormal iron accumulation around the substantia nigra (SN) is a diagnostic indicator of Parkinsonism. This study aimed to identify iron-related microarchitectural changes around the SN of brains with progressive supranuclear palsy (PSP) via postmortem validations and in vivo magnetic resonance imaging (MRI). 7 T high-resolution MRI was applied to two postmortem brain tissues, from one normal brain and one PSP brain. Histopathological examinations were performed to demonstrate the molecular origin of the high-resolution postmortem MRI findings, by using ferric iron staining, myelin staining, and two-dimensional laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging. In vivo iron-related MRI was performed on five healthy controls, five patients with Parkinson's disease (PD), and five patients with PSP. In the postmortem examination, excessive iron deposition along the myelinated fiber at the anterior SN and third cranial nerve (oculomotor nerve) fascicles of the PSP brain was verified by LA-ICP-MS. This region corresponded to those with high R2* values and positive susceptibility from quantitative susceptibility mapping (QSM), but was less sensitive in Perls' Prussian blue staining. In in vivo susceptibility-weighted imaging, hypointense pixels were observed in the region between the SN and red nucleus (RN) in patients with PSP, but not in healthy controls and patients with PD. R2* and QSM values of such region were significantly higher in patients with PSP compared to those in healthy controls and patients with PD as well (vs. healthy control: p = 0.008; vs. PD: p = 0.008). Thus, excessive iron accumulation along the myelinated fibers at the anterior SN and oculomotor nerve fascicles may be a pathological characteristic and crucial MR biomarker in a brain with PSP.

Mapping of microvascular architecture in the brain of an Alzheimer's disease mouse model using MRI.

Increasing evidence suggests that alterations in cerebral microvasculature play a critical role in the pathogenesis of Alzheimer's disease (AD). The objective of this study was to characterize and evaluate the cerebral microvascular architecture of AD transgenic (Tg) mice and compare it with that of non-Tg mice using brain microvascular indices obtained by MRI. Seven non-Tg mice and 10 5xFAD Tg mice were scanned using a 7-T animal MRI system to measure the transverse relaxation rates of R2 and R2* before and after the injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculating ΔR2* and ΔR2, the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density, mean vessel-weighted image (MvWI) and blood volume fraction (BVf) were mapped. Voxel-based analyses and region of interest (ROI)-based analyses were performed to compare the indices of the non-Tg and Tg groups. Voxel comparisons showed that BVf, mVD, VSI and MvWI were greater in the Tg group than in the non-Tg group. Additionally, the ROI-based analysis showed that ΔR2*, BVf, mVD, MvWI and VSI increased in several brain regions of the Tg group compared with those in the non-Tg group. VSI and mVD increased in Tg mice; these findings indicated microvascular disruption in the brain that could be related to damage to the neurovascular unit in AD caused by cerebral amyloid angiopathy.

Evaluation of Left Atrial Appendage Isolation Using Cardiac MRI after Catheter Ablation of Atrial Fibrillation: Paradox of Appendage Reservoir.

OBJECTIVE: To assess the effect of left atrial appendage (LAA) isolation on LAA emptying and left atrial (LA) function using cardiac MRI in patients who underwent successful catheter ablation of atrial fibrillation (AF). MATERIALS AND METHODS: This retrospective study included 84 patients (mean age, 59 ± 10 years; 67 males) who underwent cardiac MRI after successful catheter ablation of AF. According to the electrical activity of LAA after catheter ablation, patients showed either LAA isolation or LAA normal activity. The LAA emptying phase (LAA-EP, in the systolic phase [SP] or diastolic phase), LAA emptying flux (LAA-EF, mL/s), and LA ejection fraction (LAEF, %) were evaluated by cardiac MRI. RESULTS: Of the 84 patients, 61 (73%) and 23 (27%) patients showed LAA normal activity and LAA isolation, respectively. Incidence of LAA emptying in SP was significantly higher in LAA isolation (91% vs. 0%, p < 0.001) than in LAA normal activation. LAA-EF was significantly lower in LAA isolation (40.1 ± 16.2 mL/s vs. 80.2 ± 25.1 mL/s, p < 0.001) than in LAA normal activity. Furthermore, LAEF was significantly lower in LAA isolation (23.7% ± 11.2% vs. 31.1% ± 16.6%, p = 0.04) than in LAA normal activity. Multivariate analysis demonstrated that the LAA-EP was independent from LAEF (p = 0.01). CONCLUSION: LAA emptying in SP may be a critical characteristic of LAA isolation, and it may adversely affect the LAEF after catheter ablation of AF.

Serial optical coherence microscopy for label-free volumetric histopathology.

The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents.

MRI Visualization of Whole Brain Macro- and Microvascular Remodeling in a Rat Model of Ischemic Stroke: A Pilot Study.

Using superparamagnetic iron oxide nanoparticles (SPION) as a single contrast agent, we investigated dual contrast cerebrovascular magnetic resonance imaging (MRI) for simultaneously monitoring macro- and microvasculature and their association with ischemic edema status (via apparent diffusion coefficient [ADC]) in transient middle cerebral artery occlusion (tMCAO) rat models. High-resolution T1-contrast based ultra-short echo time MR angiography (UTE-MRA) visualized size remodeling of pial arteries and veins whose mutual association with cortical ischemic edema status is rarely reported. ΔR2-ΔR2*-MRI-derived vessel size index (VSI) and density indices (Q and MVD) mapped morphological changes of microvessels occurring in subcortical ischemic edema lesions. In cortical ischemic edema lesions, significantly dilated pial veins (p = 0.0051) and thinned pial arteries (p = 0.0096) of ipsilateral brains compared to those of contralateral brains were observed from UTE-MRAs. In subcortical regions, ischemic edema lesions had a significantly decreased Q and MVD values (p < 0.001), as well as increased VSI values (p < 0.001) than normal subcortical tissues in contralateral brains. This pilot study suggests that MR-based morphological vessel changes, including but not limited to venous blood vessels, are directly related to corresponding tissue edema status in ischemic stroke rat models.

Pattern recognition analysis of directional intravoxel incoherent motion MRI in ischemic rodent brains.

This study aimed to demonstrate a reliable automatic segmentation method for independently separating reduced diffusion and decreased perfusion areas in ischemic stroke brains using constrained nonnegative matrix factorization (cNMF) pattern recognition in directional intravoxel incoherent motion MRI (IVIM-MRI). First, the feasibility of cNMF-based segmentation of IVIM signals was investigated in both simulations and in vivo experiments. The cNMF analysis was independently performed for S0 -normalized and scaled (by the difference between the maximum and minimum) IVIM signals, respectively. Segmentations of reduced diffusion (from S0 -normalized IVIM signals) and decreased perfusion (from scaled IVIM signals) areas were performed using the corresponding cNMF pattern weight maps. Second, Monte Carlo simulations were performed for directional IVIM signals to investigate the relationship between the degree of vessel alignment and the direction of the diffusion gradient. Third, directional IVIM-MRI experiments (x, y and z diffusion-gradient directions, 20 b values at 7 T) were performed for normal (n = 4), sacrificed (n = 1, no flow) and ischemic stroke models (n = 4, locally reduced flow). The results showed that automatic segmentation of the hypoperfused lesion using cNMF analysis was more accurate than segmentation using the conventional double-exponential fitting. Consistent with the simulation, the double-exponential pattern of the IVIM signals was particularly strong in white matter and ventricle regions when the directional flows were aligned with the applied diffusion-gradient directions. cNMF analysis of directional IVIM signals allowed robust automated segmentation of white matter, ventricle, vascular and hypoperfused regions in the ischemic brain. In conclusion, directional IVIM signals were simultaneously sensitive to diffusion and aligned flow and were particularly useful for automatically segmenting ischemic lesions via cNMF-based pattern recognition.

MRI T2 and T2* relaxometry to visualize neuromelanin in the dorsal substantia nigra pars compacta.

Visualizing gradual changes in neuromelanin distribution within the substantia nigra is an important metric used to monitor the progression of Parkinsonism. This study aimed to identify the origin of the mismatch region between magnetic resonance transverse relaxation times (T2 and T2*) in the substantia nigra and investigate its feasibility and implications for in vivo detection of neuromelanin as a clinical biomarker. The relationships between neuromelanin distribution assessed by histological staining and the area of T2 and T2* mismatch determined by high- and low-resolution magnetic resonance relaxometry at 7T were directly compared in two normal and one depigmented substantia nigra collected at postmortem. In vivo feasibility of assessing T2 and T2* mismatch, clinically, was investigated using 3T magnetic resonance imaging. In the normal postmortem substantia nigra tissue, the T2 and T2* mismatch region exhibiting a linear pattern was strongly colocalized with neuromelanin distribution along the dorsal substantia nigra pars compacta, but a negligible amount of dorsal mismatch was observed in the depigmented brain. The regions of T2 and T2* mismatch from MRI, neuromelanin pigments from histology, and elevated iron signals from mass spectrometry were spatially overlapped for a normal postmortem brain. In preliminary in vivo studies, a similar, linear T2 and T2* mismatch region was observed in the dorsal area of the substantia nigra in eight normal subjects; this mismatch was significantly obscured in eight Parkinson's disease patients. The length of the dorsal linear mismatch line based on the T2*-T2 mask was significantly shorter in the Parkinson's disease patients compared to normal controls; this result was corroborated by reduced striatal uptake of [18F] FP-CIT dopamine transporters assessed by positron emission tomography scans. In conclusion, the measurement of T2 and T2* mismatch could serve as a complementary imaging biomarker to visualize the dorsal region of the substantia nigra pars compacta, which contains large amounts of neuromelanin.

Pattern recognition analysis of dynamic susceptibility contrast (DSC)-MRI curves automatically segments tissue areas with intact blood-brain barrier in a rat stroke model: A feasibility and comparison study.

BACKGROUND: The manual segmentation of intact blood-brain barrier (BBB) regions in the stroke brain is cumbersome, due to the coexistence of infarction, large blood vessels, ventricles, and intact BBB regions, specifically in areas with weak signal enhancement following contrast agent injection. HYPOTHESIS: That from dynamic susceptibility contrast (DSC)-MRI alone, without user intervention, regions of weak BBB damage can be segmented based on the leakage-related parameter K 2 and the extent of intact BBB regions, needed to estimate K 2 values, determined. STUDY TYPE: Feasibility. ANIMAL MODEL: Ten female Sprague-Dawley rats (SD, 200-250g) underwent 1-hour middle carotid artery occlusion (MCAO) and 1-day reperfusion. Two SD rats underwent 1-hour MCAO with 3-day and 5-day reperfusion. FIELD STRENGTH/SEQUENCE: 7T; ADC and T1 maps using diffusion-weighted echo planar imaging (EPI) and relaxation enhancement (RARE) with variable repetition time (TR), respectively. dynamic contrast-enhanced (DCE)-MRI using FLASH. DSC-MRI using gradient-echo EPI. ASSESSMENT: Constrained nonnegative matrix factorization (cNMF) was applied to the dynamic ΔR2* -curves of DSC-MRI (<4 min) in a BBB-disrupted rat model. Areas of voxels with intact BBB, classified by automated cNMF analyses, were then used in estimating K 1 and K 2 values, and compared with corresponding values from manually-derived areas. STATISTICAL TESTS: Mean ± standard deviation of ΔT1 -differences between ischemic and healthy areas were displayed with unpaired Student's t-tests. Scatterplots were displayed with slopes and intercepts and Pearson's r values were evaluated between K 2 maps obtained with automatic (cNMF)- and manually-derived regions of interest (ROIs) of the intact BBB region. RESULTS: Mildly BBB-damaged areas (indistinguishable from DCE-MRI (10 min) parameters) were automatically segmented. Areas of voxels with intact BBB, classified by automated cNMF, matched closely the corresponding, manually-derived areas when respective areas were used in estimating K 2 maps (Pearson's r = 0.97, 12 slices). DATA CONCLUSION: Automatic segmentation of short DSC-MRI data alone successfully identified areas with intact and compromised BBB in the stroke brain and compared favorably with manual segmentation. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1369-1381.